Identification of the Functional Autophagy-Regulatory Domain inHCLS1-Associated Protein X-1 That Resists Against Oxidative Stress
| Autor: | Xiang Gao, Ying-Lan Li, Guan-Sheng Liu, Wenfeng Cai, Yigang Wang, Lei Wang, Shi-Zheng Wu, Christian Paul, Lin Jiang, Boyu Wang |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Autophagosome Original Research ArticlesOrganelles/Autophagy/Apoptosis Cell Survival Apoptosis Oxidative phosphorylation Biology Mitochondrion medicine.disease_cause 03 medical and health sciences Protein Domains Downregulation and upregulation Autophagy Genetics medicine Humans Molecular Biology Adaptor Proteins Signal Transducing Membrane Potential Mitochondrial Endoplasmic reticulum Cell Biology General Medicine Cell biology Oxidative Stress HEK293 Cells 030104 developmental biology Oxidative stress Intracellular Signal Transduction |
| Zdroj: | DNA and Cell Biology. 37:432-441 |
| ISSN: | 1557-7430 1044-5498 |
| Popis: | HCLS1 Associated Protein X-1 (HAX1) promotes cell survival through attenuation of the damaged signals from endoplasmic reticulum and mitochondria, which are known as prominent intracellular compartments for the autophagic process under stress conditions. This study investigates whether autophagy can be upregulated in response to HAX1 overexpression and identifies the functional motif in HAX1 responsible for the autophagic induction. Autophagosome accumulation, mitochondrial membrane potential (Δψm), and apoptosis were assessed in HEK293 cells post transduction with full-length or truncated HAX1-encoding genes, while empty vector-transduced cells served as control. Upon the oxidative stress, the enhanced autophagy induction was observed in cells overexpressing HAX1, as well as HAX1 truncations that encode peptide segments ranging from amino acids 127-180 (AA127-180). This protective response was further supported by flow cytometry and Western Blot results, in which oxidative stress-induced Δψm dissipation and the programmed cell death were suppressed in HAX1-overexpressing cells, associated with reduced DNA fragmentation and decreased Caspase-9 cleavage. Interestingly, the HAX1-induced autophagy response was abrogated when AA127-180 was removed, compromising the antiapoptotic effects upon oxidative stress. Overall, these data indicate that autophagy induction is involved in HAX1-induced cell protective mechanism, and AA127-180 serves as the functional autophagy-regulatory domain of this antiapoptotic protein. |
| Databáze: | OpenAIRE |
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